title: The exon 3 polymorphism of the growth hormone receptor is a severity-related factor for osteoporosis.
abstract: The purpose of this study was to investigate the association between the GHR exon 3 fl/d3 polymorphism and body composition traits in Brazilian cohorts of normal post-menarche adolescent girls and in post-menopausal women with and without osteoporosis. First, multiplex PCR and quantitative PCR (TaqMan) were used with 105 DNA samples from the general Brazilian population to validate the SNP rs6873545 as a surrogate marker for the GHR polymorphism. Subsequently, genotyping was carried out to evaluate associations for this polymorphism in 136 post-menarche adolescents and 175 post-menopausal women, who were evaluated for body composition traits such as bone mineral density and fat-free mass. Statistical analysis used an independent sample t test, one-way ANOVA test and post hoc Tukey HSD test. Significant values were assumed by p < 0.05. Genotyping indicated complete linkage disequilibrium between the GHR polymorphism and the SNP alleles (r(2) = 1.0). Adolescents and healthy post-menopausal women showed no genotype associations for body composition traits or osteoporosis. However, a lower total body bone mineral density was observed in fl/fl post-menopausal women with osteoporosis (p = 0.0004). These results suggest that the SNP rs6873545 can be used as a surrogate for the GHR fl/d3 polymorphism due to linkage disequilibrium in the Brazilian population and that the fl/fl genotype is a severity-related risk factor for osteoporosis, but did not appear to be associated with disease status.
authors.affiliation: Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, SGAN 916, Asa Norte, Brasília, DF, 70790-160, Brazil, felipe.marques@catolica.edu.br.
authors.forename: Felipe Albuquerque
authors.initials: FA
authors.lastname: Marques
authors.forename: Túlio Cesar
authors.initials: TC
authors.lastname: Lins
authors.forename: Ricardo Moreno
authors.initials: RM
authors.lastname: Lima
authors.forename: Rômulo Maia Carlos
authors.initials: RM
authors.lastname: Fonseca
authors.forename: Nanci Maria
authors.initials: NM
authors.lastname: de França
authors.forename: Ricardo Jacó
authors.initials: RJ
authors.lastname: de Oliveira
authors.forename: Maria Teresinha
authors.initials: MT
authors.lastname: de Oliveira Cardoso
authors.forename: Rinaldo Wellerson
authors.initials: RW
authors.lastname: Pereira
authors.forename: Robert
authors.initials: R
authors.lastname: Pogue
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000886:Anthropometry; D001823:Body Composition / Q000235:genetics* / Q000502:physiology; D015519:Bone Density / Q000235:genetics* / Q000502:physiology; D001938:Brazil / Q000453:epidemiology; D002352:Carrier Proteins; D002648:Child; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008572:Menarche / Q000502:physiology; D008593:Menopause / Q000235:genetics; D008875:Middle Aged; D010024:Osteoporosis / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D017978:Receptors, Growth Factor; C051815:somatotropin-binding protein